美国克利夫兰诊所Michael Lincoff团队研究了索马鲁肽与非糖尿病肥胖患者心血管结局的相关性。2023年11月11日出版的《新英格兰医学杂志》发表了这项成果。

索马鲁肽是一种胰高血糖素样肽-1受体激动剂，已被证明可以降低糖尿病患者发生心血管不良事件的风险。在没有糖尿病的情况下，索马鲁肽是否能降低与超重和肥胖相关的心血管风险尚不清楚。

在一项多中心、双盲、随机、安慰剂对照、事件驱动的优越性试验中，研究组招募了45岁及以上的患者，这些患者之前患有心血管疾病，体重指数（体重除以身高的平方）为27或更大，但没有糖尿病病史。将患者按1:1的比例随机分配，每周皮下注射一次剂量为2.4 mg的索马鲁肽或安慰剂。在首次事件时间分析中，主要心血管终点是心血管原因死亡、非致命性心肌梗死或非致命性中风的复合终点。还对安全性进行了评估。

共有17604名患者入组；8803名患者被分配接受索马鲁肽治疗，8801名患者接受安慰剂治疗。索马鲁肽或安慰剂暴露的平均（±SD）持续时间为34.2±13.7个月，随访的平均持续时间为39.8±9.4个月。索马鲁肽组8803名患者中有569名（6.5%）发生主要心血管终点事件，安慰剂组8801名患者中701名（8.0%）发生（危险比为0.80；P<0.001）。索马鲁肽组1461名患者（16.6%）和安慰剂组718名患者（8.2%）发生了导致试验产品永久停药的不良事件（P<0.001）。

研究结果表明，在已有心血管疾病和超重或肥胖但没有糖尿病的患者中，每周皮下注射2.4 mg的索马鲁肽在平均随访39.8个月时，在降低心血管原因死亡、非致命性心肌梗死或非致命性中风风险方面优于安慰剂。

附：英文原文

Title: Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes | NEJM

Author: anonymous

Issue&Volume: 2023-11-11

Abstract:

Background

Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to reduce the risk of adverse cardiovascular events in patients with diabetes. Whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes is unknown.

Methods

In a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, we enrolled patients 45 years of age or older who had preexisting cardiovascular disease and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 27 or greater but no history of diabetes. Patients were randomly assigned in a 1:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis. Safety was also assessed.

Results

A total of 17,604 patients were enrolled; 8803 were assigned to receive semaglutide and 8801 to receive placebo. The mean (±SD) duration of exposure to semaglutide or placebo was 34.2±13.7 months, and the mean duration of follow-up was 39.8±9.4 months. A primary cardiovascular end-point event occurred in 569 of the 8803 patients (6.5%) in the semaglutide group and in 701 of the 8801 patients (8.0%) in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001). Adverse events leading to permanent discontinuation of the trial product occurred in 1461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in the placebo group (P<0.001).

Conclusions

In patients with preexisting cardiovascular disease and overweight or obesity but without diabetes, weekly subcutaneous semaglutide at a dose of 2.4 mg was superior to placebo in reducing the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke at a mean follow-up of 39.8 months.

DOI: 10.1056/NEJMoa2307563

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2307563